Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non–muscle-invasive bladder cancer (HR-NMIBC) with <i>FGFR3/2</i> alterations (<i>alt</i>) in THOR-2: Cohort 2 interim analysis results.
Authors: James W.F. Catto, Ben Tran, Viraj A. Master, Morgan Roupret, Geraldine Pignot, Andrea Tubaro, Nobuaki Shimizu, Nikhil Vasdev, Jürgen E. Gschwend, Yohann Loriot, Hiroyuki Nishiyama, Joan Redorta, Siamak Daneshmand, Yuji Miura, Vahid Naini, Lauren Crow, Spyros Triantos, Mahadi Baig, Gary D. Steinberg
Journal: Journal of Clinical Oncology (2023)

503 Background: Pts presenting with NMIBC carcinoma in situ (CIS) have a high risk of progression. FGFR inhibition may benefit CIS pts with FGFRalt who are unresponsive to first-line BCG, for whom treatment (tx) options, other than radical cystectomy, are limited. Erdafitinib (erda), an oral selective pan-FGFR tyrosine kinase inhibitor, is approved for locally advanced or metastatic urothelial cancer in adults with FGFR3/2alt who have progressed during or after ≥1 line of platinum-containing chemotherapy. THOR-2 (NCT04172675) is a multicohort phase 2 study of erda in pts with HR-NMIBC. Here we report results from an exploratory cohort of pts with BCG-unresponsive CIS with FGFRalt with or without papillary disease (Cohort 2). Methods: Inclusion criteria: age ≥18 y, with histologically confirmed, BCG-unresponsive HR-NMIBC with FGFR3/2alt (by local/central testing) presenting as CIS, with or without a papillary tumor and who refused or were not eligible for cystectomy. In this cohort, pts received continuous oral erda 6 mg once daily without uptitration in 28-d cycles (dose selected to improve tolerability while maintaining activity to prevent disease recurrence, for this population). Erda was discontinued if no complete response (CR) was observed within 3 mos. Exploratory efficacy end points are CR rates at the Cycle 3 Day 1 (C3D1) disease evaluation and the Cycle 6 Day 1 (C6D1) disease evaluation; safety was a key secondary end point. Results: As of the data cutoff (Sep 2022) (median follow-up of 10 mos), 10 pts have received erda (enrolled population; median age 72 y [range 52-83]; 90% CIS [1 pt with Ta was mis-enrolled]). Pts received erda for a median duration 5.9 mos (range 1.1-17.0). Of 10 enrolled pts, the CR rates at first evaluation (C3D1) and second evaluation (C6D1) were 100% (9/9 evaluable pts) and 75% (6/8 evaluable pts), respectively. The median duration of response was 3.0 mos. The most common tx-emergent adverse events (TEAEs) were dry mouth (60%; n=6), hyperphosphatemia (50%; n=5), dysgeusia (50%; n=5), and diarrhea (50.0%; n=5). 1 pt (10%) had Gr 2 retinal detachment which led to tx discontinuation and 1 pt (10%) had Gr 1 subretinal fluid; both reported as resolved. Gr ≥3 tx-related TEAEs occurred in 3 pts (30%), and included dry mouth, stomatitis, nail disorder, onychomadesis, acute kidney injury, chronic kidney disease, sepsis, and hypotension in 1 pt each. 1 pt (10%) had serious tx-related TEAEs (dry mouth, hypotension, pneumonitis, acute kidney injury, and sepsis), and 1 pt (10%) discontinued tx due to a tx-related TEAE. No tx-related deaths were observed. Conclusions: Data from Cohort 2 of THOR-2 demonstrate efficacy at C3D1 and C6D1 evaluations in pts with HR-NMIBC with FGFRalt. Safety data were consistent with the known safety profile of erda. Clinical trial information: NCT04172675 .